Ross S A, Ahrens R A, De Luca L M
Differentiation Control Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
J Cell Physiol. 1994 May;159(2):263-73. doi: 10.1002/jcp.1041590210.
The teratocarcinoma-derived F9 cells respond to retinoic acid (RA) and RA plus dibutyrylcyclic adenosine monophosphate (dcAMP) by differentiating into endoderm cells, which elaborate a laminin and type IV collagen-rich matrix. We found that the induction of differentiation is accompanied by a small but consistent increase in cell adhesiveness to a variety of substrates, including laminin. Therefore we investigated biochemical mechanisms involved in this phenomenon. Endoglycosidase treatment showed that laminin contains complex and hybrid oligosaccharide structures. RA enhanced general biosynthesis of laminin without a specific increase in galactose incorporation: this sugar was mainly in polylactosamine structures in the A chain of laminin and as terminal galactose alpha 1,3 galactose in the B chain. Laminin receptor analysis showed that RA decreased laminin binding protein-37 (LBP-37) but increased the amount of beta 1 integrin, suggesting the involvement of beta 1 integrin in the attachment process. Northern blot analysis showed increased expression of retinoid receptors within hours of RA exposure. These studies demonstrate that RA increases cell to substrate interactions by increasing the biosynthesis of laminin and beta 1 integrin. These effects are most likely subsequent to the RA-induced biosynthesis of the retinoid receptors.
畸胎癌衍生的F9细胞对视黄酸（RA）以及RA加二丁酰环磷酸腺苷（dcAMP）作出反应，分化为内胚层细胞，这些细胞会形成富含层粘连蛋白和IV型胶原的基质。我们发现，分化的诱导伴随着细胞对包括层粘连蛋白在内的多种底物的黏附性出现小幅但持续的增加。因此，我们研究了参与这一现象的生化机制。内切糖苷酶处理表明，层粘连蛋白含有复杂和杂合的寡糖结构。RA增强了层粘连蛋白的总体生物合成，但半乳糖掺入量没有特异性增加：这种糖主要存在于层粘连蛋白A链的多乳糖胺结构中，以及B链中的末端半乳糖α1,3半乳糖中。层粘连蛋白受体分析表明RA降低了层粘连蛋白结合蛋白-37（LBP-37），但增加了β1整合素的量，这表明β1整合素参与了黏附过程。Northern印迹分析表明，在暴露于RA数小时内，类视黄醇受体的表达增加。这些研究表明，RA通过增加层粘连蛋白和β1整合素的生物合成来增加细胞与底物的相互作用。这些效应很可能是在RA诱导类视黄醇受体生物合成之后出现的。
